Atrial fibrillation: Effective strategies using the latest tools

Patient complaints—or incidental findings—can prompt a Dx

Fatigue is the most common symptom of AF. Other signs and symptoms include palpitations, dyspnea, HF, hypotension, syncope, chest pain, and stroke. Some patients are asymptomatic, and AF is an incidental finding when an irregular pulse is discovered during a physical examination. The diagnosis is confirmed by electrocardiogram (EKG), telemetry, Holter monitor, event recorder, or an implanted electrocardiographic recording device. A chest x-ray, serum electrolyte levels, a complete blood count, thyroid testing, and renal and hepatic function testing are recommended. Transthoracic echocardiography to measure cardiac function, detect underlying structural heart disease, and evaluate atrial size is essential.⁵

Warfarin remains the only recommended anticoagulation strategy for patients with severe renal impairment or valvular atrial fibrillation.

An electrophysiologic (EP) study may be needed for diagnosis or treatment if another arrhythmia is present. Aberrant conduction may cause AF to present as a wide complex tachycardia and be mislabeled as ventricular tachycardia. The presence of delta waves is an indication for an EP study targeting the WPW accessory pathway. Transesophageal echocardiography (TEE) is the most sensitive and specific test for left atrial thrombi. If you are considering a TEE for a patient with AF of unknown, or >48 hours’, duration who has not been anticoagulated in the preceding 3 weeks, obtain it before performing cardioversion because of the risk of embolism.⁵

Stroke prevention

The ACC/AHA/HRS AF guideline recommends basing anticoagulation decisions on thromboembolic risk, regardless of AF pattern (paroxysmal, persistent, or permanent) (Class I recommendation).⁵ For patients with nonvalvular AF and atrial flutter, the guideline recommends using the Birmingham 2009 schema (CHA₂DS₂-VASc score) (TABLE 1^15-18) to estimate thromboembolic risk.^5,15 CHA₂DS₂-VASc improves on the older CHADS₂ score by significantly reducing the number of patients categorized as having intermediate risk and better identifying truly low-risk patients who are unlikely to benefit from anticoagulation.^16,17,19

Men with a CHA₂DS₂-VASc score of zero and women with a score of one do not need anticoagulation.^5,20 Discuss the risks and benefits of oral anticoagulation with men who have a score of one. In these intermediate-risk men, antiplatelet therapy with aspirin and/or clopidogrel may be reasonable, especially if there is an indication other than stroke prevention (eg, post-myocardial infarction). Oral anticoagulation is strongly recommended for all patients with a CHA₂DS₂-VASc score of 2 or higher.^5,18,21,22

Anticoagulant considerations: Warfarin vs DOACs

Warfarin was the gold standard for stroke prevention in nonvalvular AF until the direct oral anticoagulants (DOACs) became available in 2010. Guidelines in the United States and the United Kingdom recommend shared decision-making to help patients with AF who do not have a specific indication for warfarin choose between warfarin and the DOACs.^5,21 Canadian and European guidelines recommend DOACs as the first-line option for anticoagulation and reserve warfarin for patients who have contraindications to, or are unable to afford, DOACs.^18,22 All current guidelines recommend continuing warfarin in patients who are stable, well controlled, and satisfied with warfarin therapy and the monitoring and dietary restrictions it entails.

DOACs are as effective as warfarin. All of the DOACs are approved for stroke prevention based on individual phase III non-inferiority trials in which they were compared to warfarin.^23-26 In addition, a meta-analysis of these 4 trials involving a total of 71,683 patients (mean age 70-73 years; median follow-up, 1.8-2.8 years) evaluated the benefits and risks of the 4 DOACs against the former gold standard.²⁷

Higher doses of the DOACs (dabigatran 150 mg BID, rivaroxaban 20 mg/d, edoxaban 60 mg/d, and apixaban 5 mg BID) reduced the rates of stroke or systemic embolism (relative risk [RR]=0.81; 95% confidence interval [CI], 0.73-0.91; P<.0001; number needed to treat [NNT]=147), hemorrhagic stroke (RR=0.49; 95% CI, 0.38-0.64; P<.0001; NNT=219), and all-cause mortality (RR=0.90; 95% CI, 0.85-0.95; P=.0003; NNT=128), compared with warfarin.²⁷ It is important to note that while lower doses of some DOACs (dabigatran 110 mg BID and edoxaban 30 mg/d) were not as effective at preventing ischemic stroke when compared with warfarin (RR=1.3; 95% CI, 1-1.6; P=.045), they still significantly reduced hemorrhagic stroke (RR=0.33; 95% CI, 0.23-0.46; P<.0001) and all-cause mortality (RR=0.89; 95% CI, 0.83-0.96; P=.003).

Of course, the biggest concern is bleeding. In that same meta-analysis, the difference in major bleeding events with DOACs vs warfarin was not statistically significant (RR=0.86; 95% CI, 0.73-1; P=.06). While DOACs likely lower rates of intracranial hemorrhage (RR=0.48; 95% CI, 0.39-0.59; P<.0001; NNT=132), they seem to increase the risk of gastrointestinal (GI) bleeding (RR=1.3; 95% CI, 1-1.6; P=.043; number needed to harm [NNH]=185).²⁷

Without head-to-head trials, it is impossible to know if one direct oral anticoagulant is superior to another.

There was significant heterogeneity in the GI bleeding outcome, however. When compared with warfarin, GI bleeding was increased by dabigatran 150 mg BID (RR=1.5; 95% CI, 1.2-1.9; P<.001) and edoxaban 60 mg/d (HR=1.2; 95% CI, 1.02-1.5; P=.03), but there were no significant differences for dabigatran 110 mg BID or apixaban 5 mg BID.^23,25,26

On the other hand, edoxaban 30 mg/d had a lower risk of GI bleeding when compared with warfarin (HR=0.67; 95% CI, 0.53-0.83; P<.001).²⁵ Without head-to-head trials, it is impossible to know if one DOAC is superior to another. Apixaban 5 mg BID appears to offer the best overall balance between efficacy and safety. Other DOACs may be better options for patients who have specific concerns regarding efficacy or safety.^28,29

Convenience, interactions, and cost may be the deciding factors. Since all DOACs are fairly comparable in efficacy and safety, other factors such as convenience, interactions with other medications, and cost should be considered when deciding on a medication for an individual patient (TABLE 2^30,31). The DOACs require no lab monitoring or dose titration, and all 4 have fewer potential drug interactions than warfarin.³⁰ Due to their relatively short half-lives, strict adherence is critical; DOACs are not suitable for patients who frequently miss doses.⁵ (For more information on starting or switching to DOACs, see, “Is a novel anticoagulant right for your patient?” J Fam Pract. 2014;63:22-28.)

A word about DOACs and renal impairment. Another concern with DOACs is their reliance on renal metabolism and excretion. A meta-analysis of the 4 phase III trials of the DOACs, this time involving 58,338 patients, evaluated DOAC efficacy and safety compared to warfarin in the presence of kidney dysfunction.³² Renal function was categorized as normal (estimated glomerular filtration rate [eGFR] >80 mL/min/1.73 m²), mildly impaired (eGFR 50-80 mL/min/1.73 m²), or moderately impaired (eGFR <50 mL/min/1.73m²). Compared with warfarin, DOACs lowered stroke risk in patients with mild (RR=0.71; 95% CI, 0.62-0.81) or moderate (RR=0.79; 95% CI, 0.66-0.94) renal impairment. DOACs also reduced major bleeding compared to warfarin in patients with mild (RR=0.88; 95% CI, 0.80-0.97) or moderate (RR=0.80; 95% CI, 0.66-0.94) renal impairment. How the DOACs fare in patients with severe renal dysfunction could not be determined because such patients were excluded from the trials.

Keep in mind that the DOACs require dose adjustment at different levels of renal impairment (TABLE 2^30,31), and warfarin remains the only recommended treatment for patients with severe renal impairment, according to both AHA/ACC/HRS and European Society of Cardiology guidelines.^5,18